ORIGINAL ARTICLE
http://dx.doi.org/10.4306/pi.2015.12.3.367
Print ISSN 1738-3684 / On-line ISSN 1976-3026 OPEN ACCESS
Microstructural Changes of Anterior Corona Radiata in Bipolar Depression I. Fatih Karababa1, Huseyin Bayazıt1, Nihat Kılıçaslan2, Mustafa Celik3, Hasan Cece2, Ekrem Karakas2, and Salih Selek4,5 1
Department of Psychiatry, Faculty of Medicine, University of Harran, Sanliurfa, Turkey Department of Radiology, Faculty of Medicine, University of Harran, Sanliurfa, Turkey 3 Department of Psychiatry, Diyarbakir Training and Research Hospital, Diyarbakir, Turkey 4 Department of Psychiatry, Faculty of Medicine, University of Medeniyet, Istanbul, Turkey 5 Department of Psychiatry and Behavioral Sciences, Harris County Psychiatric Center, The University of Texas Health Science Center at Houston, Houston, TX, USA 2
ObjectiveaaIn bipolar disorder, dysregulation of mood may result from white matter abnormalities that change fiber tract length and fi-
ber density. There are few studies evaluating the white matter microstructural changes in bipolar I patients (BD) with depressive episodes. The present study aimed to evaluate anterior corona radiata in BD patients with depressive episode using Diffusion Tensor Imaging (DTI). MethodsaaTwenty-one patients with bipolar depression and 19 healthy controls were investigated and groups were matched for age and gender. Diffusion-weighted echoplanar brain images (DW-EPI) were obtained using a 1.5 T MRI scanner. Regions of interest (ROIs) were manually placed on directional maps based on principal anisotropy. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of white matter were measured in the anterior corona radiata (ACR) bilaterally by diffusion tensor imaging. ResultsaaThere was not a significant difference between groups of age and gender (p>0.05). Significantly lower FA was observed in bilateral ACR in bipolar patients with depression compared with healthy individuals. And there is significantly higher ADC values in the left frontal corona radiate in bipolar patients. ConclusionaaWhite matter abnormalities can be detected in patients with BD using DTI. The neuropathology of these abnormalities is unclear, but neuronal and axonal loss, myelin abnormalities and reduced white matter fiber density are likely to be relevant. Psychiatry Investig 2015;12(3):367-371 Key WordsaaDiffusion tensor imaging, Anterior corona radiate, Bipolar disorder, Depression, White matter.
INTRODUCTION Bipolar I disorder (BD) is comprised by periods of depressed, elevated or irritable mood. Despite much research into BD, the underlying neural pathophysiology of BD remains unclear and reliable biomarkers are few. Neuroimaging markers such as decreased activation and gray matter content and increased activation in the parahippocampal gyrus extending to the thalamus, and the caudate nucleus and some peripheral biochemiReceived: May 5, 2014 Revised: August 22, 2014 Accepted: August 28, 2014 Available online: July 6, 2015 Correspondence: Salih Selek, MD
Department of Psychiatry, Faculty of Medicine, University of Medeniyet, D-100 Mevkii, 34700 Kadikoy, Istanbul, Turkey Tel: +90 (216) 566 6600-4331, Fax: +90 (216) 3183192, E-mail:
[email protected] cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
cal compounds such as BDNF, oxidative stress related compounds, cytokines, etc. are appealing candidates.1-3 It is found that bipolar disorder patients have effectively shorter WM fiber tracts and comparatively reduced WM fiber density in a major tract connecting limbic system structures to the frontal lobe.4 A breakdown in the architecture of normal WM tracts which connect brain regions involved in emotion regulation has been reported.5 Diffusion Tensor Imaging (DTI) is neuroimaging technique to elucidate the abnormalities of white matter tissue in the brain. DTI presents the opportunity to measure the organization of fibers within specific white matter tracts even when macrostructural changes are absent.6 Noninvasive mapping of white matter tracts using DTI is potentially useful in enlightening anatomical connectivity in the human brain. There are several parameters indicating microstructural integrity of white matter such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). FA is scalar measure derived by DTI and it Copyright © 2015 Korean Neuropsychiatric Association 367
Bipolar Depression and Neuropathology
reflects the directional coherence of water diffusion and is sensitive to microstructural WM differences in integrity and organization. FA is defined on a scale ranging from mostly isotropic (FA value nearing 0) indicating poor integrity of the axons to mostly anisotropic (FA value nearing 1) indicating intact WM.7 Lower diffusion anisotropy is commonly observed concurrent with CNS pathology.8 Apparent diffusion coefficient (ADC) as a scalar index of the rate of water diffusion among different diffusion directions under a Gaussian distribution.9 A high value of ADC indicates less restricted diffusion and implies the presence of fewer organized structures in the white matter which supporting the presence of abnormalities in the structural integrity of white matter in bipolar disorder. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. A significantly lower fractional anisotropy (FA) was observed in the corona radiata and in the genu of corpus callosum, right inferior and left superior longitudinal fasciculus and significantly higher apparent diffusion coefficient (ADC) in the frontal lobe in bipolar patients showing WM microstructural alterations.3,10-12 Several researches have shown that there may be microstructural WM alterations even in remitted BP patients.11,13,14 Few DTI researches have focused on BD patients with depressive episode. Benedetti et al.15 found lower FA in WM tracts of the genu of corpus callosum, bilateral anterior corona radiata and in right superior and posterior corona radiate in Bipolar depression. Zanetti et al.16 found decreased FA in ventromedial prefronto-limbic-striatal WM in Bipolar depressive patients compared to bipolar remitted patients. The anterior corona radiate (ACR) is part of the limbic-thalamo-cortical circuitry and includes thalamic projections from the internal capsule to the cortex including those prefrontal cortex gray matter areas that have been associated with impaired top-down emotion regulation systems.17-19 Since ACR is the “crossroads” of those pathways it may be involved with bipolar depression. Therefore, the present study aimed to evaluate anterior corona radiata in BD patients with depressive episode by DTI.
orders (Axis II disorders), alcohol and substance abuse disorders, and severe head injury. After complete description of the study to the subjects, a written informed consent was obtained from all subjects. Ethics committee of the Harran University Medical School approved the trial. A semi-structured form was used to detect several sociodemographic and clinical variables such as gender, age, co-morbid conditions. The patients who had co-morbid axis I or II conditions due to DSM-IV criteria were excluded from the study. Additionally pregnancy, severe systemic diseases, epilepsy, diabetes mellitus, hypertension, drug and alcohol dependence, severe head injury, were the exclusion criteria of the study. Mood symptoms were evaluated in all participants on the day of the scan using the Turkish version of Young Mania Rating Scale (YMRS) and the Turkish version of 21-item Hamilton Depression Rating Scale (HDRS) by one psychiatrist.20,21 Bipolar participants were eligible if they had a YMRS score lower than or equal to 7, a 21-item HDRS score higher than 7, and had been depressive by self-report.22 All images were obtained on a 1.5 Tesla MRI scanner (Magnetom, Symphony-Quantum, Siemens, Erlangen, Germany). Initially, 3D T1-weighted MP-RAGE images of the whole brain was acquired (matrix 256×256, FOV 250 mm, number of partitions 172 for a nominal slice thickness of 1 mm, Average=4 slices, 0 mm gap). Finally, axial DTI scans were acquired with a pulsed gradient, double spin echo, EPI sequence (TR/TE=3100/ 98 ms, 128×128 matrix, FOV 230 mm, b=1000 s/mm2, Average=4 slices, 5 mm slice thickness, 0 mm gap). The images were transferred to a computer workstation (Leonardo, Siemens Medical Solutions, Forcheim, Germany). Regions of interest (ROIs) were manually placed on directional maps based on principal anisotropy (Figure 1). The FA and ADC values of white matter were measured in the anterior corona radiata bilaterally. The measurements were obtained by two experienced ra-
METHODS Twenty-one participants with a DSM-IV diagnosis of Bipolar I Disorder, who were on depressive episode at the time of enrollment, were recruited through Harran University Research Hospital, Psychiatry Clinic. Nineteen healthy volunteer controls were enrolled from the hospital staff. Patient and control groups have similar distribution in age, sex and smoking status. Exclusion criteria for all participants included a history of chronic systemic diseases such as diabetes mellitus, hypertension, neurological illness, metal implants, pregnancy, personality dis-
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Figure 1. Region of interest placement for diffusion tensor imaging analysis.
IF Karababa et al. Table 1. Sociodemographic and clinical characteristics of the patients and controls
BD patients Age (mean±SD)
Controls p value
34±10.75
Gender (male/female)
34.42±9.43
6/15
8/11
4.7±4.7
12±4
Duration of illness (years)
11.8±7.3
N/A
Ham-D total scores
19.2±4.8
N/A
Duration of education (years)
Number of episodes
0.896 0.370
